Improved early event-free survival with imatinib in Philadelphia chromosome - Positive acute lymphoblastic leukemia: A Children's Oncology Group Study

Kirk R. Schultz, W. Paul Bowman, Alexander Aledo, William B. Slayton, Harland Sather, Meenakshi Devidas, Chenguang Wang, Stella M. Davies, Paul S. Gaynon, Michael Trigg, Robert Rutledge, Laura Burden, Dean Jorstad, Andrew Carroll, Nyla A. Heerema, Naomi Winick, Michael J. Borowitz, Stephen P. Hunger, William L. Carroll, Bruce Camitta

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Abstract

Purpose: Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome - positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups. Patients and Methods: We evaluated whether imatinib (340 mg/m2/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph- ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) -identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT. Results: Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% ± 11% (95% CI, 64% to 90%), more than twice historical controls (35% ± 4%; P < .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88% ± 11%; 95% CI, 66% to 96%) or sibling donor BMT (57% ± 22%; 95% CI, 30.4% to 76.1%). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction. Conclusion: Imatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT.

Original languageEnglish
Pages (from-to)5175-5181
Number of pages7
JournalJournal of Clinical Oncology
Volume27
Issue number31
DOIs
StatePublished - 1 Nov 2009

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    Schultz, K. R., Bowman, W. P., Aledo, A., Slayton, W. B., Sather, H., Devidas, M., Wang, C., Davies, S. M., Gaynon, P. S., Trigg, M., Rutledge, R., Burden, L., Jorstad, D., Carroll, A., Heerema, N. A., Winick, N., Borowitz, M. J., Hunger, S. P., Carroll, W. L., & Camitta, B. (2009). Improved early event-free survival with imatinib in Philadelphia chromosome - Positive acute lymphoblastic leukemia: A Children's Oncology Group Study. Journal of Clinical Oncology, 27(31), 5175-5181. https://doi.org/10.1200/JCO.2008.21.2514